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Side effects are worse when we think medication looks expensive

Watch the cost. People are more likely to experience stronger side effects when a treatment appears to be more expensive, according to a study of the nocebo effect.

While the placebo effect means that some people feel better when they have unknowingly been given a sham or control treatment, the nocebo works the opposite way. Researchers frequently observe nocebo effects in clinical trials, when people who receive a placebo experience negative side effects as if they had been given an actual drug.

Placebos are known to have stronger positive effects the more expensive the person receiving them believes them to be. Alexandra Tinnermann, at the University Medical Center Hamburg-Eppendorf, and her colleagues wondered if price might also affect the strength of the nocebo effect.

The team created two packages for fake creams and told volunteers that they are used to treat itchy skin. One package looked like an expensive pharmaceutical brand name, while the other looked like a cheaper, generic medication.

The participants were shown one of the two creams and told that it was believed to increase a person’s sensitivity to pain as a side effect.

Pain sensitivity

The team then applied creams to participants’ arms, and exposed their limbs to increasing levels of heat. Each person was asked to rank the discomfort they felt.

The participants given the more expensive-looking cream reported more pain than those given the cheaper-looking cream. Relative to a control cream that was described as having no active ingredients, the generic-looking cream raised pain on average by around 3 per cent, while the expensive-looking cream increased pain by nearly 30 per cent.

The finding confirms that the price of a treatment effects not only placebo strength, but nocebo power too.

During the pain test, the team collected fMRI images of the brain, brainstem and spinal cord. They found that activity in a particular area of the prefrontal cortex and a region called the periaqueductal gray varied depending on what cream had been given. Both these areas are part of the neural pain pathway, and have also been implicated in mediating placebo effects.

The findings may help refine how doctors nurses and pharmacists talk to patients about medications, enabling them to try to minimize the nocebo effect, says Tinnermann.